A phase Ib/II trial with expansion of patients at the MTD trial of olaparib plus weekly (metronomic) carboplatin and paclitaxel in relapsed ovarian cancer patients.

5573 Background: We established the olaparib tablet maximum tolerated dose, dose limiting toxicities (DLT’s) and response to therapy of carboplatin, paclitaxel and olaparib tablet given simultaneously, reported at ASCO 2014. This abstract will include data from both the phase 1b and the phase 2 expansion. Methods: A total of 54 subjects were evaluated in this trial, 14 in phase 1b and 40 in phase 2. Eligibility required measurable disease, adequate organ function and ECOG performance status of ≤ 2. Subjects had to have failed first line platinum containing chemotherapy. BRCA testing was conducted as available. Subjects received the metronomic therapy of paclitaxel 60mg/m2 IV and carboplatin AUC 2 IV weekly, 3 weeks out of 4, and olaparib tablets at the MTD of 150 mg bid administered orally for 3 consecutive days (D1-D3), every week for each cycle. Subjects were assessed for toxicity and response according to the protocol. Subjects that reached a confirmed complete remission were transitioned to olaparib tablets only, 300 mg bid, until disease progression. Results: Median age was 58 and median number of prior regimens was 4. There have been no deaths due to the study regimen. One patient had grade 4 neutropenia and an allergic reaction to carboplatin. The common grade 3 toxicities caused by this regimen were neutropenia, anemia and thrombocytopenia. Two subjects had mild GI toxicities. There was no evidence of cardiac, hepatic, or pulmonary toxicities in any of these subjects. 22.5% of subjects had a complete remission (CR), 30% had PR, 25% had SD and 22.5% had PD. Of the 9 CR’s, 6 were gBRCA mutated. PFS median for gBRCA mutated subjects is 19 months vs 4 months for non-mutated gBRCA subjects. OS median for gBRCA mutated subjects is 24 months vs 16 months for gBRCA non-mutated subjects. All of the CR’s are alive. Conclusions: Olaparib tablets can be safely administered simultaneously with a weekly regimen of carboplatin and paclitaxel in heavily pretreated ovarian cancer subjects. Olaparib appears to be highly effective in gBRCA mutated. This is the first successful combination of olaparib tablets with carboplatin and paclitaxel that has been well tolerated. Clinical trial information: NCT01650376.